FGF2 signaling is associated with poor disease outcome and anti–estrogen resistance in patients with ER+ breast cancer. (A) MCF-7 and T47D cells were pretreated with 1 µM fulv for 24 h and then treated with or without 25 ng/ml FGF2 for 1 h in triplicate, and RNA sequencing was performed to generate a signature of FGF2 response. Heatmap of differentially expressed genes common between MCF-7 and T47D (P < 0.05) in response to FGF2 treatment. (B–E) RNA-sequencing data were used to derive FGF2 pathway activation scores for each human primary breast tumor from four independent datasets containing information from 1,390 (B), 164 (C), 298 (D), and 202 (E) patients. Patients with tumors exhibiting positive versus negative scores were compared by log-rank test using RFS (B–D) or OS (E).